Irritable bowel syndrome (IBS) is a chronic medical condition which affects 10-15% of the population in industrialized countries. IBS is associated with a profound impairment of patient's quality of life, significant loss of productivity, and $2 billion in direct health care costs in the US alone, mainly due to unsatisfactory treatment. Patient heterogeneity in terms of disease pathogenesis, symptom expression and psychological co-morbidities are among the factors implicated in the variation of therapeutic responses. Therefore, the need to develop biological markers that can distinguish patients likely to benefit most from specific forms of treatment, and as importantly, from a placebo treatment, is imperative. We have recently concluded a 6 week randomized clinical trial in IBS patients (n=262) to examine the effects of placebo and acupuncture treatments, compared to a natural history control group. Blood samples were collected at baseline and at 3 and 6 weeks of follow-up. The positive results of this trial and sample availability allow us to perform a secondary Omics analysis examining patient variability in response to treatment. Our primary hypothesis is that serum proteins participate directly or indirectly to the brain-gut interactions associated with clinical responses in IBS. Our second hypothesis is that patients who clinically respond to placebo or acupuncture treatment have distinct serum protein profiles from those who don't respond. A third hypothesis is that placebo or acupuncture treatment results in changes in the serum proteome. We will incorporate various high throughput experimental approaches, some of them targeted to specific biological pathways and others leading to unbiased discoveries, to pursue the goals of this study. The serum proteomics analysis will be complemented with an investigation of common polymorphisms in genes of interest that emerge. Findings stemmed from such studies could lead to improvement of inclusion/exclusion criteria in randomized clinical trials based on biological screens. In terms of personalized medicine, findings could result in methodologies to enhance medication responses, adjust the doses or select medications with fewer side effects.